1. Field of the Invention
The present invention relates generally to the preparation of mistletoe extracts and methods for making such extracts in a medicinally useful and pharmaceutically acceptable form. More particularly, the present invention relates to methods for making and using mistletoe extracts wherein certain marker proteins are utilized to control the quality and clinical use of the extracts. These marker proteins provide a measure of the extracts effectiveness in treating certain diseases. The extract is either accepted or rejected as a pharmaceutical grade composition depending upon the amounts and/or biological activity of the various protein markers which are present in the extract and the intended clinical use.
2. Description of Related Art
Mistletoe belongs to the genus Viscum (family, Loranthaceae) which includes a variety of semiparasitic plants found all over the world. Mistletoe is a parasite which grows on a variety of deciduous trees including apple, cherry, oak, ash hawthorn, lime and acorn. Mistletoe and extracts of mistletoe have been used for centuries in a wide variety of therapeutic settings. The effectiveness of mistletoe as a remedy for treating a multitude of ailments has been the subject of a great deal of folklore, superstitions and mystical accounts. Although many of the early uses for mistletoe may have been based more on fantasy than on fact, the reputation of mistletoe as a powerful elixir is well deserved because this parasitic plant contains a rather large variety of complex and pharmacologically potent ingredients.
Beginning in the early 1900's, mistletoe and the pharmacological properties of extracts from mistletoe have been subjected to a more rigorous scientific investigation. In particular, mistletoe extracts have been suggested for use in treating a variety of specific diseases including cardiovascular illnesses, especially hypertension and arteriosclerosis; cancer and arthrosis. Fermented mistletoe extracts marketed under the tradenames ISCADOR.RTM., HELIXOR.RTM. and PLENOSOL.RTM. have been proposed for use in treating a number of specific diseases. ISCADOR.RTM. and HELIXOR.RTM. have been injected subcutaneously while PLENOSOL.RTM. has been administered both intracutaneously and intravenously. These three commercially available preparations are derived from mistletoe found in Europe, Viscum album L.
Since 1980, the investigation of mistletoe has increased due to its immunomodulatory properties and potential usefulness in treating cancer. See International Journal of Cancer Research Treatment-ONCOLOGY--Vol. 43, Supplement 1, 1986. A major problem facing mistletoe investigators involves the analysis, identification and standardization of the pharmacologically active ingredients in mistletoe and extracts thereof. This problem is exacerbated by the fact that the numerous complex ingredients which are found in mistletoe extracts vary widely in type and amount depending upon the species of mistletoe, the location where the plant is grown, the time of year when the plant is harvested, the particular host tree, the extraction procedure used and a number of other factors.
The principal classes of ingredients in mistletoe which have been found to provide pharmacological activity include lectins, phenylpropans, viscotoxins, alkaloids, flavonoids, lignans, amines, phenyl carboxylic acids and polysaccharides. Although the types of pharmacologically important compounds which are generally present in mistletoe have been identified, investigators have not had a great deal of success with respect to standardizing the multitude of available extracts to establish if one or more ingredients are responsible for the observed bioactivity and whether the ingredients act together or may be effective individually. The extremely diverse nature of mistletoe extracts and the inherent variability in extract compositions makes it difficult to use the extracts to conduct clinical investigations. Standardization of the pharmaceutical agent is essential in order to produce meaningful clinical data. Further, identification and standardization of the active ingredients in mistletoe extracts are also important in the routine treatment of patients. It is imperative that the mistletoe extract be of consistent and verifiable quality to insure that dosage levels and treatment protocols are effective.
As is apparent from the above, mistletoe and extracts prepared therefrom are potent pharmacological agents which require further investigation. As part of this continuing investigation of the medicinal and pharmacological properties of the numerous mistletoe varieties from around the world, there is a need to provide standardization of the quality of mistletoe extracts. Further, it is essential that the extracts which are used in various clinical studies and treatment protocols also be standardized and that quality control programs be instituted.